Lu-Tex is a photosensitizer with an absorption peak at 732 nm, a wavelength capable of penetrating tissue and melanin. Patients with unresectable metastatic cancer of the skin or subcutaneous tissue received a single IV injection of Lu-Tex, followed 3-8 hours later by light treatment of lesions (732 nm, 75 mW/cm2, 150 J/cm2). Lu-Tex doses were escalated from 0.5 to 6.2 umol/kg in 7 cohorts. Light was delivered by a laser or light emitting diode. From 12/95 to 11/96, 35 patients received 44 treatments. Histologies were breast (15), melanoma (7), Kaposi's sarcoma (5), basal cell (2), squamous cell (2). Grade 3/4 toxicities were (patient number) pain (5), headache (1), and hypertension (1). Dose limiting toxicities were pain in the treatment field during treatment and dysesthesias in light exposed areas. Other toxicities included moderate pain during treatment, transient paresthesias or numbness of non-illuminated areas, and rare mild photosensitivity. Responses were observed at all Lu-Tex doses. Response after a single treatment (104 lesions, 22 evaluable patients) were, by lesion, 26% complete (CR), 18% partial (PR), overall 44%, and, by patient, 18% CR, 27% PR, overall 45%. Response was notable in breast cancer (by lesion (n=38): 47% CR, 29% PR, overall 76%; by patient (n=12): 33% CR, 33% PR, overall 66% and melanoma (by lesion (n=25): 28% CR, 8% PR, overall 36%; by patient (n=3): 33% PR. 5 of 6 patients receiving a second treatment had an improvement in response (3 PR achieved CR, 2 stable disease achieved PR). Photodynamic therapy with Lu-Tex is well tolerated and has activity in breast cancer and melanoma. Phase II studies in breast cancer will be underway shortly.